Cells Lacking Pfh1, a Fission Yeast Homolog of Mammalian Frataxin, Display Constitutive Activation of the Iron Starvation Response.

Universitat Pompeu Fabra, Spain.
Friedreich ataxia is a genetic disease caused by deficiencies in frataxin. This protein has homologues not only in higher eukaryotes, but also in bacteria, fungi and plants. The function of this protein is still controversial. We have identified a frataxin homolog in fission yeast, and have analyzed whether its depletion leads to any of the phenotypes observed in other organisms. Cells deleted in pfh1 are sensitive to growth under aerobic conditions, display increased levels of total iron, hallmarks of oxidative stress such as protein carbonylation, decreased aconitase activity and lower levels of oxygen consumption compared to wild-type cells. This mitochondrial protein seems to be important for iron and/or reactive oxygen species homeostasis. We have analyzed the proteome of cells devoid of Pfh1, and determined that gene products up- and down-regulated upon iron depletion in wild-type cells are constitutively misregulated in this mutant. Due to the particular signalling pathway components governing the iron starvation response in fission yeast, our experiments suggest that cells lacking Pfh1 display a decrease of cytosolic available iron which triggers activation of Grx4, the common regulator of the iron starvation gene expression program. Our Schizosaccharomyces pombe pfh1 strain constitutes a new and useful model system to study Friedreich ataxia.
J. Biol. Chem. Oct. 31, 2012; 0(0); [PUBMED:23115244]
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